innate immunity эмч нар

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ÝÌØÈÓÑ, Áèî-Àíàãààõûí ñóðãóóëü Áè÷èë àìü-Äàðõëàà ñóäëàëûí òýíõèì Äàðõëàà ñóäëàë Áàéãàëèéí äàðõëàà /ºâºðìºö áóñ/

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Page 1: innate immunity эмч нар

ÝÌØÈÓÑ, Áèî-Àíàãààõûí ñóðãóóëü

Áè÷èë àìü-Äàðõëàà ñóäëàëûí òýíõèì

Äàðõëàà ñóäëàë

Áàéãàëèéí äàðõëàà

/ºâºðìºö áóñ/

Page 2: innate immunity эмч нар

Äàðõëàà òîãòîëöîîíû õºãæèë

erypl

mye

neu mφ

lym

nk

thy

CD8+

CD4+

CTL

TH2

TH1

Page 3: innate immunity эмч нар

Дархлааны хариу урвалын бүрэлдэхүүн

Page 4: innate immunity эмч нар

Дархлааны хариу урвалын бүрэлдэхүүн

Epithelial barriers Innate immune system Adaptive immune system

Receptors

Diversity

Specificity

Distribution

Self/nonself

discrimination

Pattern-recognition receptors

Low diversity

Broad specificity for PAMPs

that are common to many

pathogens

On epithelial cell surfaces

(non clonal distribution)

No specificity for self

Pattern-recognition receptors

Low diversity

Broad specificity for PAMPs

that are common to many

pathogens

In blood and on cell surfaces

of innate immune cells (non

clonal distribution)

No specificity for self

Antigen receptors

Infinite diversity

Restricted specificity for

antigens that are unique to

particular pathogens

On cell surfaces of

lymphocytes (clonal

distribution)

Possible specificity for self

Action time Immediate ImmediateSlow on first contact

Rapid on repeated contact

Memory No No Yes

Page 5: innate immunity эмч нар

Дархлааны хариу урвалын бүрэлдэхүүн

Page 6: innate immunity эмч нар

Өвөрмөц бус хамгаалах тогтолцоо

Page 7: innate immunity эмч нар

Çàëãèóð ýñ ….

Influenced by

the work of

Eli Metchnikoff,

George Bernard Shaw:

“Àëèâàà ýìãýãèéí òºãñ ýì÷ëýõ

¿íäýñ íü …. Çàëãèóð ýñèéã

èäýâõæ¿¿ëýõýä îðøèíî. Ýìèéí

¿ð ä¿í áîë õóóðàì÷.

…Çàëãèóð ýñèéã

èäýâõæ¿¿ëýõ íü òºãñ

ýì÷ëýõèéí ñóóðü áîëíî…”

Page 8: innate immunity эмч нар

ªâºðìºö áóñ ýñ¿¿ä õýðõýí òàíèãäàõ

âý?

Pathogen-associated molecular patterns

(PAMPs)

PAMPs íü ýìãýãòºðºã÷èéí á¿òýö

– Ýçýí ýñýä òîäîðõîéëîãäîõã¿é

– Ýìãýãòºðºã÷äºä ýëáýã òàðõñàí

– Õàðüöàíãóé òîãòâîðòîé á¿òýöòýé (influenza

viruses ãåìàããëþòèíèí áà íåéðîàìèíèäàçà бусад)

Page 9: innate immunity эмч нар

PAMPs (1)

Ãðàì-ïîçèòèâ áàêòåðèéí Ðeptidoglycan

Ãðàì íåãàòèâ áàêòåðèéí LPS (endotoxin)

ds-RNA

Ìåòèëæýýã¿é DNA

Öýëìýí áà øèëá¿¿ð

Page 10: innate immunity эмч нар

PAMPs (2)

PAMPs ìèêðîáûí àìüäðàëûí óõàë

õýñýã.

– LPS: áàêòåðèéí õàíàíû á¿òöèéí á¿ðäýë

õýñýã

– dsRNA: ðåïëèêàöèä øààðäëàãàòàé

Page 11: innate immunity эмч нар

PAMPs-òàé õîëáîãäîõ ðåöåïòîð

Pattern Recognition Receptors

(PRRs)

– Ìèêðîáûí ìîëåêóëûí 103 á¿òöèéã òàèíà. (cf.

ªâºðìºö äàðõëààíû ýñèéí ðåöåïòîð õàðèéí

àíòèãåíèé 107 á¿òöèéã òàíèíà.)

Page 12: innate immunity эмч нар

PRRs: 3 á¿ëýãòýé

1. ßëãàðäàã ìîëåêóë

– õàâñàðãà

– Màííîç õîëáîõ ëåêòèí (MBL)

– C-óðâàëæ óóðàã (CRP)

– LPS-õîëáîõ óóðàã (LBP)

2. Залгиур эсийн рецептор

- Фагоцитоз-Ñýã ò¿¿ãч ðåöåïòîð /Scavenger

receptors/

- эндоцитоз

3. Цитокины ялгаралтын рецептор

Page 13: innate immunity эмч нар

Öèòîêèíû ÿëãàðàëòû㠺人õ ðåöåïòîð

Toll-like receptors (TLRs)– Ýìãýãòºðºã÷òýé õîëáîãäñîí TLR Ẻìèéí NF-

kB /òðàíñêðèïöèéí õ¿÷èí ç¿éë/ èäýâõæèõ äîõèî äàìæèëòûã ýõë¿¿ëíý.

– NF-kB íü ýðãýýä ¿ðýâñëèéí öèòîêèíû ãåíèéã èäýâõæ¿¿ëíý

TNF-a

IL-1

chemokines

Page 14: innate immunity эмч нар
Page 15: innate immunity эмч нар
Page 16: innate immunity эмч нар

Ôàãîöèòîç …

Attachment via

IgG FcR

ScavengerR

CR

Toll-like R

Page 17: innate immunity эмч нар

Çàëãèñàí íÿíã óñòãàõ ìåõàíèçì

myloperoxidase-independent myeloperoxidase-dependent

oxygen-depenedent oxygen-independent

Intracellular Killing

Page 18: innate immunity эмч нар

Ýôôåêòîð ìîëåêóë ¯éë

Õ¿÷èëòºðºã÷ ¿ë õàìààðàëò õàéëóóëàõ

ìåõàíèçì

Êàòèîíò óóðàã (êàòåïñèí) Ìèêðîáûí ìåìáðàíûã ãýìòýýíý

Ëèçîöèì Ýñèéí õàíàíû ìóêîïåïòèäûã

ãèäðîëèçä îðóóëíà

Ëàêòîôåððèí Íÿíãèéí òºìðèéã íýãä¿¿ëíý

Ãèäðîëèòèê ôåðìåíò (ïðîòåàçà Çàëãèñàí íÿíã õàéëóóíà

Page 19: innate immunity эмч нар

Íåéòðîôèëèéí ìºõëºãèéí øèíæ

Àíõäàã÷ ìºõëºã

Êàòèîíò óóðàã, ëèçîöèì, äåôåíñèí, ïðîòåàçà, áà ìèåëîïåðîêñèäàçà

Õî¸ðäîã÷ ìºõëºã

Ëèçîöèì, NADPH îêñèäàçà, ëàêòîôåððèí áà Â12-õîëáîîò óóðàã

Çàëóó íåéòðîôèëä

àçóðîôèë ìºõëºã

äàâàèãàéëíà

Áîëîâñîðñîí íåéòðîôèëä

ºâºðìºö

Page 20: innate immunity эмч нар

Íåéòðîôèë íü õàëäâàðûí ¿åä

SOS äîõèî– N-ôîðìèë ìåòèîíèí

– Á¿ëýãíýëòèéí ñèñòåì

– Õàâñàðãûí á¿ðäýë

Çàëãèóð ýñèéí óðâàë– Ñóäàñíû íààëäàìõàé

– Äèàïåä

– Õåìîòàêñèñ

– Èäýâõæèõ

– Ôàãîöèòîç áà óñòãàõ

Page 21: innate immunity эмч нар

ªâºðìºö áóñ óñòãàã÷ ýñ

NK áà LAK cells

ADCC (K) ýñ

Èäýâõæñýí

ìàêðîôàã

Ýîçèíîôèë

Õàðèéí àíòèãåí áîëîí

ººðèéí “áàé”

ººð÷ëºãäñºí ýñèéí

óñòãàíà

Page 22: innate immunity эмч нар

Natural Killer (NK) ýñ

Òîì ìºõëºãò ëèìôîöèò ãýæ

íýðëýíý (LGL)

Âèðóñýýð õàëäâàðëàñàí ýñ áà

õàâäðûí ýñèéã óñòãàíà

Ãàäàðãóóä íü CD56 & CD16

èëýðíý õàðèí CD3 èëðýõã¿é

IL2 áa IFN-γ-ð èäýâõæèæ LAK

ýñ áîëíî

Page 23: innate immunity эмч нар

Ëèìôîêèíýýð èäýâõæñýí óñòãàãñ

ýñ (LAK)

kills

malignant

cells

Õàâäðûí ýñ

òðàíñôîðìàöèä

îðñîí ýñèéã

óñòãàíà

Page 24: innate immunity эмч нар

NK ýñèéí çîõèöóóëãà

MHC I KIR KAR KAL

No Killing Killing

Page 25: innate immunity эмч нар

Ê ýñ

Ìîðôîëîãîîð ÿëãààã¿é

IgG Fc ðåöåïòîðòîé

Ýñðýãáèåýýð õó÷èãäñàí

áèåòèéã òàíèíà

NK ýñ (IgG), ìàêðîôàã

(IgG), ýîçèíîôèë (IgE) áà

áóñàä ýñ (IgG)

Page 26: innate immunity эмч нар

Өвөрмөц бус хамгаалах шингэний хүчин зүйлс

Цитокин:

• Цусны эсүүдийн эдэд

цуглуулах- хемотаксис

• Вирүсийн репликацыг

саатуулах

• Өвөрмөц дархлааг

эхлүүлэх

• Хурц үеийн уургуудын

нийлэгшилийг өдөөх

Page 27: innate immunity эмч нар

• Эерэг хурц үеийн уургууд:

•С-урвалж уураг,

•манноз холбоот уураг,

•хавсрага,

•ферритин,

•церулоплазмин,

•ийлдсийн амилойд А уураг,

•гаптоглобин,

•альфа2-макроглобин

• Сөрөг хурц үеийн уургууд:

•альбумин,

•трансферрин,

•транстиретин,

•ретинол холбоот уураг,

•антитромбин,

•Транскортин эдгээрийн

хэмжээ багасах нь үрэвслийн

эрчмийг илэрхийлнэ.

Өвөрмөц бус хамгаалах шингэний

хүчин зүйлс- Хурц үеийн уургууд

Page 28: innate immunity эмч нар

Õàâñàðãà

1894 îíä Bordet àíõ íýýñýí

Øèíý èéëäýñ õàéëóóëàõ

èäýâõòýé áîëîõûã

àæèãëàñàí

Ýíý õàéëóóëàõ èäýâõ íü

56îC-ò 30 ìèí õàëààõàä

àëäàãäàæ áàéæýý.

Page 29: innate immunity эмч нар

Õàâñàðãûí èäýâõ

Ýåðýã ¿ð ä¿í:

Íÿíã õó÷èæ ôàãîöèòîçûã äýìæèíý

Çàëãèóð ýñèéã èäýâõæ¿¿ëæ òàíüöûãíýìýãä¿¿ëíý

Áàêòåðè áà õàëäâàðëàãäñàí ýñèéãõàéëóóëíà

Ýñðýãáèåèéí óðâàëûã õÿíàíà

Äàðõàí á¿ðäëèéã çàéëóóëàõàä îðîëöîíî

Àïîïòîçîä ºðòñºí ýñèéã çàéëóóëíà

Ѻðºã ¿ð ä¿í:

¿ðýâñýë, àíàôèëàêñè

Page 30: innate immunity эмч нар

Õàâñàðãûí òîãòîëöîîíû óóðãóóä(íýðøèë)

C1(qrs), C2, C3, C4, C5, C6, C7, C8, C9

B, D, H áà I õ¿÷èí ç¿éë, ïðîïåðäèí (P)

Ìàííîç õîëáîõ ëåêòèí (MBL), MBL õàìààðàëò ñåðèí

ïðîòåàçà (MASP-1 MASP-2)

C1 ñààòëóóð (C1-INH, ñåðïèí), C4-õîëáîõ óóðàã

(C4-BP), decay accelerating factor (DAF),

C1 ðåöåïòîð (CR1), S-óóðàã (âèòðîíåêòèí)

Page 31: innate immunity эмч нар

Õàâñàðãà èäýâõæèõ çàì

Ñîíãîìîë çàì Àëüòåðíàòèâ çàì

Ñ5 èäýâõæèíý

Ìåìáðàí Äîâòëîã÷ Á¿ðäýë

Ýñðýãáèå õàìààðàëò

Ëåêòèíû çàì

Эсрэгбие үл хамааралт

C3 èäýâõæèõ áà

Ñ5 êîíâåðòàçà ¿¿ñíý

Page 32: innate immunity эмч нар